Cardiovascular disease is a leading cause of death in the human population. This is especially true in developed countries, where the increasing incidence of obesity is considered to be the major contributing factor to cardiovascular and related diseases. For example, the incidence of heart disease as a cause of death was 12.4% in all World Health Organization States, whereas in the U.S., heart attacks account for nearly 30% of deaths. In addition, other disease states related to or exacerbated by impairment of cardiovascular function make cardiovascular diseases the single greatest contributor to death and disability.
The underlying issue in cardiovascular disease is the development of atherosclerosis, a disease that affects vessels of the arterial circulation. It is characterized as a chronic inflammatory response in the walls of blood vessels, in part due to deposition of lipoproteins, in particular low density lipoproteins (LDLs), as well as infiltration by macrophages. Atherosclerosis is known to begin early in life (during childhood) with the rate of progression dependent on a variety of factors including diet, exercise, and genetic predisposition.
The earliest morphologically identifiable stage of plaque development is termed a fatty streak, which in fact is an accumulation of macrophages that have ingested oxidized LDL in the vessel wall, giving them the appearance of fat in the muscular tissue that forms the vessel wall. These macrophages ingest oxidized LDL in the plaque, accumulating numerous cytoplasmic vesicles—these macrophages become known as foam cells. Over time the fatty streak evolves to become an established plaque characterized by further accumulation of macrophages and the local accumulation of an inflammatory infiltrate. Eventually foam cells die, releasing their contents into the plaque, which further exacerbates the inflammatory reaction. In addition, cytokines released by damaged endothelial cells lead to smooth muscle proliferation and migration from the vessel media to the intima, leading to the development of a fibrous capsule that covers the plaque. Over time, calcification at the margins of the plaque can occur.
It has been known for some time that over time that progressive enlargement of atherosclerotic plaques eventually leads to a narrowing of the lumen of afflicted vessels. Traditionally, narrowing of 75% or greater has been considered clinically significant. However, more recently it has been discovered that events such as heart attacks can occur even when there is no sign of significant narrowing of vessels, due to the inherent instability of some plaques.
It is now known that plaques can be structurally unstable, and spontaneously rupture. When a plaque ruptures, tissue fragments and plaque contents are released into the lumen of the blood vessel, resulting in a clotting response. While the clot is effective to cover and stabilize the rupture, it intrudes into the lumen of the vessel, reducing luminal diameter, and obstructing blood flow, thus creating a stenotic region. If the compromise to flow is significant, for example where the clot completely or nearly completely occludes the lumen, ischemia can occur in tissues downs stream from the site of the blockage. Where the vessel is a coronary artery, this can lead to a myocardial infarction. Should the blockage occur in a cerebral artery stroke is possible. Significantly, the majority of fatal events occur from ruptures in areas where there is little prior narrowing, although it is recognized that over time repeated ruptures of plaques will lead to stenosis, and eventually downstream ischemia, with the same clinical outcome.
Because of the risk posed by unstable plaque, there is now a recognized need to detect atherosclerotic plaque, and in particular soft, or vulnerable plaque, prior to the patient becoming symptomatic. Earlier detection of vulnerable plaque can be especially useful in order to begin a course of treatment that can reduce the risk of a sudden ischemic event due to plaque rupture, or due to the gradual development of stenotic regions in a vessel as can occur over time, or to reopen areas of vessel that have become substantially occluded. Typically, treatment of stenosis in sensitive areas such as the heart or the brain has been accomplished by angioplasty techniques. Maintaining patency of vessels has become easier with the advent of vascular stent devices.
In the past, detection and diagnosis of atherosclerosis has been difficult. For example, according to data in the U.S. from 2004, the first symptom of cardiovascular disease in over half of those so diagnosed, is heart attack or sudden death. Unfortunately, by the time obvious symptoms arose, the disease is usually quite advanced with the result that treatment options and clinical outcome can be limited. The recognition of contributing factors such as the effect of cholesterol intake, obesity, and smoking, has led to an awareness of the benefit of preventative lifestyle choices in reducing the risk of developing atherosclerosis.
More recently, advances have also been made in both the diagnosis and treatment of cardiovascular disease. For example, 64 slice CT technology now makes it possible to evaluate the extent cardiovascular disease through detection of calcifications in vessels. In addition, CT protocols are also available that make it possible to visualize vulnerable plaque. Thus, it is becoming easier to detect atherosclerosis at earlier and earlier stages, providing an ever increasing window of opportunity to treat the disease at as early a stage as possible.